The long-term objective of this research is to elucidate mechanisms of visual excitation. The specific aim of this project is to identify and isolate a Drosophila gene which, if defective, affects visual transduction. The methodology used to achieve this goal will be a combination of molecular genetics, biochemistry and electrophysiology. Analysis of this gene is expected to provide important information about photoreceptor function. In addition, the techniques used are some of the most powerful ones currently available; similar techniques may be used for the diagnosis and, ultimately, for the treatment of certain disorders of the visual system. According to a current model of visual transduction, the receptor potential of an invertebrate photoreceptor is generated by the superimposition of discrete events known as "bumps". Each bump is produced by the absorption of a single photon and this bump is a membrane voltage change caused by an increased membrane conductance to sodium ions. With increasing light intensity, the rate of occurrence of the bumps becomes higher and the bumps become smaller (adapt) to result in the increasingly smoother receptor potential. In the Drosophila mutant trp (transient receptor potential), the receptor potential decays to near baseline during an intense, prolonged stimulus. As the receptor potential decays, individual bumps can be seen to occur. It seems that in this mutant, unlike in the wild type, the rate of bump occurrence does not increase proportionally with light intensity. Therefore, the defective trp gene appears to affect, selectively, the mechanisms associated with the rate of bump occurrence. The trp mutation is fully recessive and has been mapped to the third chromosome, in subdivision 99C. A cloned DNA segment has been shown to map, by in situ hybridization, to a unique site in 99C. This will enable cloning of the entire chromosomal region ascribed to trp by sequential isolation of overlapping genomic clones. Once the trp gene is isolated, the gene product can be identified with the cloned DNA and its role in visual transduction can then be studied in molecular detail.